Expression signatures of exosomal long non-coding RNAs in urine serve as novel non-invasive biomarkers for diagnosis and recurrence prediction of bladder cancer

Yao Zhan,Weili Duan,Yunshan Wang,Lutao Du,Keqiang Yan,Lili Wang,Xiumei Jiang,Shujun Zhang,Juan Li,Lishui Wang,Chuanxin Wang,Yinghui Zhao

doi:10.1186/s12943-018-0893-y

Abstract

Recently, expression signatures of exosomal long non-coding RNAs (lncRNAs) have been proposed as potential non-invasive biomarkers for cancer detection. In this study, we aimed to develop a urinary exosome (UE)-derived lncRNA panel for diagnosis and recurrence prediction of bladder cancer (BC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to screen and evaluate the expressions of eight candidate lncRNAs in a training set (208 urine samples) and a validation set (160 urine samples). A panel consisting of three differently expressed lncRNAs (MALAT1, PCAT-1 and SPRY4-IT1) was established for BC diagnosis in the training set, showing an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.854. Subsequently, the performance of the panel was further verified with an AUC of 0.813 in the validation set, which was significantly higher than that of urine cytology (0.619). In addition, Kaplan-Meier analysis suggested that the up-regulation of PCAT-1 and MALAT1 was associated with poor recurrence-free survival (RFS) of non-muscle-invasive BC (NMIBC) (p < 0.001 and p = 0.002, respectively), and multivariate Cox proportional hazards regression analysis revealed that exosomal PCAT-1 overexpression was an independent prognostic factor for the RFS of NMIBC (p = 0.018). Collectively, our findings indicated that UE-derived lncRNAs possessed considerable clinical value in the diagnosis and prognosis of BC.

Highlights

Expression signatures of exosomal long non-coding RNAs have been proposed as potential non-invasive biomarkers for cancer detection
Studies have shown that bladder cancer (BC) cells can secrete exosomes into the urine and Long non-coding RNA (lncRNA) have been found to be stably present in exosomes [5]
We established a three-lncRNA panel for BC diagnosis through analyzing urinary exosome (UE)-derived lncRNAs, and identified that PCAT-1 could act as an independent risk factor for recurrence-free survival (RFS) of non-muscle-invasive BC (NMIBC)

Summary

Introduction

Expression signatures of exosomal long non-coding RNAs (lncRNAs) have been proposed as potential non-invasive biomarkers for cancer detection. We aimed to develop a urinary exosome (UE)-derived lncRNA panel for diagnosis and recurrence prediction of bladder cancer (BC). Exosomes can act as vehicles in cell-to-cell communication by transferring oncogenic molecules and play significant roles in tumorigenesis, progression and metastasis [3]. These functional contents are not stochastically packed into exosomes, which may rely on signature motifs, leading to the variation of exosomal contents under different pathological conditions or in different original cell types [4]. We systematically analyzed the expression profiles of UE-derived lncRNAs in BC patients and established a three-lncRNA panel for BC detection. We the explored the prognostic value of the selected exosomal lncRNAs

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Conclusion